Influence of alimentary zinc deficiency on the concentration of the second messengers D-myo-inositol-1,4,5-trisphosphate (IP3) and s,n-1,2-diacylglycerol (DAG) in testes and brain of force-fed rats.

The phosphatidylinositol-specific phospholipase C, presumably a Zn-metalloenzyme, catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to inositol-1,4,5-trisphosphate (IP3) and s,n-1,2-diacylglycerol (DAG). The activity of phosphatidylinositol-specific phospholipase C was measured indirectly by determination of the metabolites IP3 and DAG in Zn deficiency. For this purpose 24 male Sprague-Dawley rats with an average live mass of 117 g were divided into 2 groups of 12 animals each. The Zn-deficient and the control group received a semisynthetic casein diet with a Zn content of 1.6 ppm and 115 ppm, respectively. In order to prevent the reduced feed intake that occurs in Zn deficiency and the associated energy and protein depletion from interfering with the experimental parameters, all animals were fed four times daily by gastric tube. This made it possible to supply all animals with adequate nutrients and to synchronize the feed intake exactly. After 12 d, the depleted rats were in a severe state of Zn deficiency, as demonstrated by the reduction of Zn in the serum and the femur by 74% and 43%, respectively, and the 28% lower serum activity of alkaline phosphatase. The radioimmunologically determined concentrations of IP3 were reduced by a significant 53% in the testes of the Zn-deficient rats (0.24 nmol IP3/g wet wt) compared to the control animals (0.51 nmol IP3/g wet wt), while the IP3 concentration in the brain was not affected by the alimentary Zn supply (1.7 and 1.6 nmol IP3/g wet wt, respectively). The DAG concentrations in the testes (474 vs 471 nmol DAG/g wet wt) and the brain (594 vs 640 nmol DAG/g wet wt), which were determined by radioenzymatic methods, showed no significant differences in relation to the alimentary Zn supply. The fact that the Zn concentration in the Zn-deficient rats was reduced only in the testes and not in the brain and that high concentrations of DAG may also result from other metabolic processes suggests that the phosphatidylinositol-specific phospholipase C in the mammalian organism is a Zn-metalloenzyme whose activity is reduced in alimentary Zn deficiency in tissues suffering Zn loss.